STRAP

STRAP
Identifiers
Aliases	STRAP, MAWD, PT-WD, UNRIP, serine/threonine kinase receptor associated protein
External IDs	OMIM: 605986; MGI: 1329037; GeneCards: STRAP
Gene location (Human)
Chr.	Chromosome 12 (human)
End	15,903,478 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	137,728,930 bp
RNA expression pattern
	Top expressed in
	secondary oocyte; ; corpus epididymis; ; pons; ; tail of epididymis; ; beta cell; ; caput epididymis; ; anterior pituitary; ; embryo; ; ventricular zone; ; ganglionic eminence;
	Top expressed in
	mandibular prominence; ; maxillary prominence; ; somite; ; seminiferous tubule; ; cumulus cell; ; abdominal wall; ; epiblast; ; primitive streak; ; hair follicle; ; ventricular zone;
	More reference expression data
	n/a
Gene ontology
Molecular function	signaling receptor binding; protein binding; RNA binding;
Cellular component	cytoplasm; SMN complex; SMN-Sm protein complex; cytosol; nucleus; nucleoplasm;
Biological process	mRNA processing; negative regulation of transcription by RNA polymerase II; negative regulation of epithelial cell migration; maintenance of gastrointestinal epithelium; negative regulation of transforming growth factor beta receptor signaling pathway; negative regulation of epithelial to mesenchymal transition; negative regulation of pathway-restricted SMAD protein phosphorylation; RNA splicing; negative regulation of epithelial cell proliferation; spliceosomal snRNP assembly;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	11171
	20901
	ENSG00000023734
	ENSMUSG00000030224
	Q9Y3F4
	Q9Z1Z2
	NM_007178
	NM_011499
	NP_009109
	NP_035629
	Wikidata
View/Edit Human	View/Edit Mouse

Serine-threonine kinase receptor-associated protein is an protein that in humans is encoded by the STRAP gene.

Structure

STRAP is a 38.5 kDa, 350-amino acid protein belonging to the WD40 repeat protein family. It contains seven WD40 repeats that fold into a seven-bladed β-propeller structure that spans almost the entire length of the protein. The N-terminal WD40 repeats binds to TGF-β receptor I, whereas the C-terminal region is phosphorylated by TGF-β receptor II.

Function

STRAP is a WD40-repeat protein that binds both the type I and type II TGF-β receptors. Its primary function is to recruit and stabilize the inhibitory Smad, SMAD7, at the activated TGF-β receptor complex.

By stabilizing this STRAP/SMAD7/TGF-β receptor complex, STRAP sterically blocks SMAD2 and SMAD3 from binding to the activated type I TGF-β receptor, preventing its phosphorylation and thus blunting TGF-β mediated up-regulation of gene expression.

Apoptosis

STRAP binds directly to ASK1 through ASK1's C-terminal domain and the fourth and sixth WD40 repeats of STRAP. This binding allows STRAP to be phosphorylated by ASK1, and the resulting complex reduces ASK1's downstream signaling to the JNK and p38 stress-response pathways. It does so by helping to stabilize ASK1's association with its own inhibitory proteins, thioredoxin and 14-3-3. It also reduces ASK1's ability to form a complex with its downstream target MKK3. Through this mechanism, STRAP protects cells from H₂O₂-induced, ASK1-driven apoptosis, favoring cell survival. STRAP has also been described as a positive regulator of PDK1 signaling.

Clinical significance

STRAP is a component of the survival motor neuron (SMN) complex, binding to it through an interaction with GEMIN7. Loss of the complex's core protein, SMN, causes spinal muscular atrophy, a childhood disorder characterized by motor neuron degeneration.

STRAP also inhibits TGF-β receptor signaling by stabilizing the inhibitory protein SMAD7, which in turn limits activation of SMAD2 and SMAD3. This pathway is frequently dysregulated in cancer and elevated STRAP expression has been reported in several tumor types, including colorectal and lung carcinoma, where it promotes proliferation and reduces apoptosis.

Interactions

STRAP has been shown to interact with:

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000023734 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030224 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Seong HA, Jung H, Ha H (April 2007). "NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and negatively regulates TGF-beta signaling". The Journal of Biological Chemistry. 282 (16): 12075–12096. doi:10.1074/jbc.m609832200. PMID 17314099.
↑ "Entrez Gene: STRAP serine/threonine kinase receptor associated protein".
↑ Karfa S, Saurav S, Feng B, Li S, Law BK, Datta PK (June 2025). "The Role of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Signaling in Cancer". Cells. 14 (12). doi:10.3390/cells14120854. PMC 12190354. PMID 40558481.
↑ Vukmirovic M, Manojlovic Z, Stefanovic B (October 2013). "Serine-threonine kinase receptor-associated protein (STRAP) regulates translation of type I collagen mRNAs". Molecular and Cellular Biology. 33 (19): 3893–3906. doi:10.1128/MCB.00195-13. PMC 3811873. PMID 23918805.
1 2 3 4 5 6 7 8 Datta PK, Moses HL (May 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology. 20 (9): 3157–3167. doi:10.1128/MCB.20.9.3157-3167.2000. PMC 85610. PMID 10757800.
↑ Halder SK, Anumanthan G, Maddula R, Mann J, Chytil A, Gonzalez AL, et al. (June 2006). "Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis". Cancer Research. 66 (12): 6156–6166. doi:10.1158/0008-5472.CAN-05-3261. PMID 16778189.
↑ Xu P, Liu J, Derynck R (July 2012). "Post-translational regulation of TGF-β receptor and Smad signaling". FEBS Letters. 586 (14): 1871–1884. doi:10.1016/j.febslet.2012.05.010. PMC 4240271. PMID 22617150.
↑ Jung H, Seong HA, Manoharan R, Ha H (January 2010). "Serine-threonine kinase receptor-associated protein inhibits apoptosis signal-regulating kinase 1 function through direct interaction". The Journal of Biological Chemistry. 285 (1): 54–70. doi:10.1074/jbc.M109.045229. PMC 2804202. PMID 19880523.
1 2 3 Manoharan R, Seong HA, Ha H (April 2018). "Dual Roles of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) in Redox-Sensitive Signaling Pathways Related to Cancer Development". Oxidative Medicine and Cellular Longevity. 2018 5241524. doi:10.1155/2018/5241524. PMC 5933018. PMID 29849900.
↑ Karfa S, Saurav S, Feng B, Li S, Law BK, Datta PK (June 2025). "The Role of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Signaling in Cancer". Cells. 14 (12): 854. doi:10.3390/cells14120854. PMC 12190354. PMID 40558481.
↑ Otter S, Grimmler M, Neuenkirchen N, Chari A, Sickmann A, Fischer U (2007). "A comprehensive interaction map of the human survival of motor neuron (SMN) complex". The Journal of Biological Chemistry. 282 (8): 5825–5833. doi:10.1074/jbc.M608528200. hdl:21.11116/0000-0007-E7EE-9. PMID 17178713.
↑ Chaytow H, Huang YT, Gillingwater TH, Faller KM (2018). "The role of survival motor neuron protein (SMN) in protein homeostasis". Cellular and Molecular Life Sciences. 75 (21): 3877–3894. doi:10.1007/s00018-018-2849-1. PMC 6182345. PMID 29872871.
↑ Datta PK, Moses HL (2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology. 20 (9): 3157–3167. doi:10.1128/MCB.20.9.3157-3167.2000. PMC 85610. PMID 10757800.
↑ Xu P, Liu J, Derynck R (2012). "Post-translational regulation of TGF-β receptor and Smad signaling". FEBS Letters. 586 (14): 1871–1884. doi:10.1016/j.febslet.2012.05.010. PMC 4240271. PMID 22617150.
↑ Karfa S, Saurav S, Feng B, Li S, Law BK, Datta PK (2025). "The Role of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Signaling in Cancer". Cells. 14 (12): 854. doi:10.3390/cells14120854. PMC 12190354. PMID 40558481.
1 2 Datta PK, Chytil A, Gorska AE, Moses HL (December 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". The Journal of Biological Chemistry. 273 (52): 34671–34674. doi:10.1074/jbc.273.52.34671. PMID 9856985.

Hunt SL, Hsuan JJ, Totty N, Jackson RJ (February 1999). "unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA". Genes & Development. 13 (4): 437–448. doi:10.1101/gad.13.4.437. PMC 316477. PMID 10049359.
Matsuda S, Katsumata R, Okuda T, Yamamoto T, Miyazaki K, Senga T, et al. (January 2000). "Molecular cloning and characterization of human MAWD, a novel protein containing WD-40 repeats frequently overexpressed in breast cancer". Cancer Research. 60 (1): 13–17. PMID 10646843.
Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, et al. (October 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research. 10 (10): 1546–1560. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
Iriyama C, Matsuda S, Katsumata R, Hamaguchi M (2001). "Cloning and sequencing of a novel human gene which encodes a putative hydroxylase". Journal of Human Genetics. 46 (5): 289–292. doi:10.1007/s100380170081. PMID 11355021.
Pillai RS, Grimmler M, Meister G, Will CL, Lührmann R, Fischer U, et al. (September 2003). "Unique Sm core structure of U7 snRNPs: assembly by a specialized SMN complex and the role of a new component, Lsm11, in histone RNA processing". Genes & Development. 17 (18): 2321–2333. doi:10.1101/gad.274403. PMC 196468. PMID 12975319.
Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL (March 2005). "Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity". Science. 307 (5715). New York, N.Y.: 1603–1609. Bibcode:2005Sci...307.1603O. doi:10.1126/science.1105718. PMID 15761148. S2CID 41013935.
Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, et al. (March 2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science. 307 (5715). New York, N.Y.: 1621–1625. Bibcode:2005Sci...307.1621B. doi:10.1126/science.1105776. PMID 15761153. S2CID 39457788.
Carissimi C, Baccon J, Straccia M, Chiarella P, Maiolica A, Sawyer A, et al. (April 2005). "Unrip is a component of SMN complexes active in snRNP assembly". FEBS Letters. 579 (11): 2348–2354. Bibcode:2005FEBSL.579.2348C. doi:10.1016/j.febslet.2005.03.034. PMID 15848170. S2CID 10276186.
Grimmler M, Otter S, Peter C, Müller F, Chari A, Fischer U (October 2005). "Unrip, a factor implicated in cap-independent translation, associates with the cytosolic SMN complex and influences its intracellular localization". Human Molecular Genetics. 14 (20): 3099–3111. doi:10.1093/hmg/ddi343. PMID 16159890.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Guo D, Han J, Adam BL, Colburn NH, Wang MH, Dong Z, et al. (December 2005). "Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress". Biochemical and Biophysical Research Communications. 337 (4): 1308–1318. Bibcode:2005BBRC..337.1308G. doi:10.1016/j.bbrc.2005.09.191. PMID 16236267.
Seong HA, Jung H, Choi HS, Kim KT, Ha H (December 2005). "Regulation of transforming growth factor-beta signaling and PDK1 kinase activity by physical interaction between PDK1 and serine-threonine kinase receptor-associated protein". The Journal of Biological Chemistry. 280 (52): 42897–42908. doi:10.1074/jbc.M507539200. PMID 16251192.
Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
Carissimi C, Saieva L, Gabanella F, Pellizzoni L (December 2006). "Gemin8 is required for the architecture and function of the survival motor neuron complex". The Journal of Biological Chemistry. 281 (48): 37009–37016. doi:10.1074/jbc.M607505200. PMID 17023415.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000023734 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030224 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Seong HA, Jung H, Ha H (April 2007). "NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and negatively regulates TGF-beta signaling". The Journal of Biological Chemistry. 282 (16): 12075–12096. doi:10.1074/jbc.m609832200. PMID 17314099.

[entrez-6] "Entrez Gene: STRAP serine/threonine kinase receptor associated protein".

[Karfa_2025-7] Karfa S, Saurav S, Feng B, Li S, Law BK, Datta PK (June 2025). "The Role of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Signaling in Cancer". Cells. 14 (12). doi:10.3390/cells14120854. PMC 12190354. PMID 40558481.

[Vukmirovic_2013-8] Vukmirovic M, Manojlovic Z, Stefanovic B (October 2013). "Serine-threonine kinase receptor-associated protein (STRAP) regulates translation of type I collagen mRNAs". Molecular and Cellular Biology. 33 (19): 3893–3906. doi:10.1128/MCB.00195-13. PMC 3811873. PMID 23918805.

[Datta_2000-9] 1 2 3 4 5 6 7 8 Datta PK, Moses HL (May 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology. 20 (9): 3157–3167. doi:10.1128/MCB.20.9.3157-3167.2000. PMC 85610. PMID 10757800.

[Halder_2006-10] Halder SK, Anumanthan G, Maddula R, Mann J, Chytil A, Gonzalez AL, et al. (June 2006). "Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis". Cancer Research. 66 (12): 6156–6166. doi:10.1158/0008-5472.CAN-05-3261. PMID 16778189.

[Xu_2012-11] Xu P, Liu J, Derynck R (July 2012). "Post-translational regulation of TGF-β receptor and Smad signaling". FEBS Letters. 586 (14): 1871–1884. doi:10.1016/j.febslet.2012.05.010. PMC 4240271. PMID 22617150.

[Jung2010-12] Jung H, Seong HA, Manoharan R, Ha H (January 2010). "Serine-threonine kinase receptor-associated protein inhibits apoptosis signal-regulating kinase 1 function through direct interaction". The Journal of Biological Chemistry. 285 (1): 54–70. doi:10.1074/jbc.M109.045229. PMC 2804202. PMID 19880523.

[Manoharan2018-13] 1 2 3 Manoharan R, Seong HA, Ha H (April 2018). "Dual Roles of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) in Redox-Sensitive Signaling Pathways Related to Cancer Development". Oxidative Medicine and Cellular Longevity. 2018 5241524. doi:10.1155/2018/5241524. PMC 5933018. PMID 29849900.

[Karfa2025-14] Karfa S, Saurav S, Feng B, Li S, Law BK, Datta PK (June 2025). "The Role of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Signaling in Cancer". Cells. 14 (12): 854. doi:10.3390/cells14120854. PMC 12190354. PMID 40558481.

[15] Otter S, Grimmler M, Neuenkirchen N, Chari A, Sickmann A, Fischer U (2007). "A comprehensive interaction map of the human survival of motor neuron (SMN) complex". The Journal of Biological Chemistry. 282 (8): 5825–5833. doi:10.1074/jbc.M608528200. hdl:21.11116/0000-0007-E7EE-9. PMID 17178713.

[16] Chaytow H, Huang YT, Gillingwater TH, Faller KM (2018). "The role of survival motor neuron protein (SMN) in protein homeostasis". Cellular and Molecular Life Sciences. 75 (21): 3877–3894. doi:10.1007/s00018-018-2849-1. PMC 6182345. PMID 29872871.

[17] Datta PK, Moses HL (2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology. 20 (9): 3157–3167. doi:10.1128/MCB.20.9.3157-3167.2000. PMC 85610. PMID 10757800.

[18] Xu P, Liu J, Derynck R (2012). "Post-translational regulation of TGF-β receptor and Smad signaling". FEBS Letters. 586 (14): 1871–1884. doi:10.1016/j.febslet.2012.05.010. PMC 4240271. PMID 22617150.

[19] Karfa S, Saurav S, Feng B, Li S, Law BK, Datta PK (2025). "The Role of Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Signaling in Cancer". Cells. 14 (12): 854. doi:10.3390/cells14120854. PMC 12190354. PMID 40558481.

[Datta_1998-20] 1 2 Datta PK, Chytil A, Gorska AE, Moses HL (December 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". The Journal of Biological Chemistry. 273 (52): 34671–34674. doi:10.1074/jbc.273.52.34671. PMID 9856985.